Search

When unbalanced faults such as single-phase voltage drop occur in the power grid, VSC-HVDC will fail or become unstable due to sudden changes in amplitude, phase, frequency, etc. of the power grid voltage. Therefore, the role of PLL in a non-ideal power grid is particularly important, but often PLL needs to make a compromise between dynamic response and system stability. Therefore, this paper proposes a free-PLL control strategy under non ideal power grid. First, according to the power transmission model of VSC-HVDC under power grid imbalance, the control command required by the inverter is given, which is determined in the environment free-PLL. Therefore, PLL is not required to retrace the phase of the grid voltage. In addition, in order to overcome the impact of the sudden change of power grid frequency on the free-PLL strategy, a frequency locking strategy is proposed in the free-PLL environment, the response time is about 1 grid cycle. Finally, in order to verify the effectiveness and correctness of the proposed strategy, the VSC-HVDC system’s active power transmission stability is guaranteed when the grid voltage encounters different degrees of single-phase sags.

The electron re-injection effect has revealed the great probability rate of photon generation due to the head-on collision between relativistic electrons and laser. We study the electron re-injection dynamics when the ultra-intense laser irradiates the near-critical-density plasma and successfully controls the photon radiation by means of the transversely tailored plasma. Starting from the relativistic corrected ponderomotive force, the critical strength of the laser field required by the refluxing effect is theoretically obtained. Then, the theoretical description of the wavefront formed by electron refluxing is given via plugging in the difference in the transverse phase velocity of the plasma wave. Simulation results display a curved surface of the refluxing electrons, which are in good agreement with the calculation results stemming from the physics model. The re-built phase space of the refluxing electrons illustrates that they gain energy mainly from the longitudinal electrostatic field on the re-injection path. Despite the energy of the refluxing electron being relatively low, it could radiate more photons via more efficient non-linear Compton scattering than the electron being accelerated in the positive direction. Furthermore, we employ a transverse density profile in the plasma and successfully achieve control of the electron re-injection effect and the properties of the resultant photons as well. Simulation results exhibit that overcritical electron beams are successively re-injected from the plasma density peaks. These backward electrons emit photons along the two maximal plasma densities as they collide with the laser pulse. Although the quality of the photons is not improved, their spatial distribution is changed, which is a big step toward manipulating light sources.

We present a novel scheme for dense electron acceleration driven by the laser irradiation of a near-critical-density plasma. The electron reflux effect in a transversely tailored plasma is particularly enhanced in the area of peak density. We observe a bubble-like distribution of re-injected electrons, which forms a strong quasistatic electromagnetic field that can accelerate electrons longitudinally while also preserving the electron transverse emittance. Simulation results demonstrate that over-dense electrons could be trapped in such an artificial bubble and accelerated to an energy of ∼500MeV. The obtained relativistic electron beam can reach a total charge of up to 0.26 nC and is well collimated with a small divergence of 17 mrad. Moreover, the wavelength of electron oscillation is noticeably reduced due to the shaking of the bubble structure in the laser field. As a result, the energy of the produced photons is substantially increased to the γ range. This new regime provides a path to generating high-charge electron beams and high-energy γ-ray sources.

Despite advances in NiCr + Cr3C2–NiCr coating improving the erosion wear resistance at low impact angles, the deterioration at medium and high impact angles has not been solved for the impeller subjecting to multi–impact angle. Herein the conflict is circumvented by combining the erosion performance of the NiCr and Cr3C2–NiCr under different impact angles and proposing a novel coating structure. First, the NiCr + Cr3C2–NiCr coating specimens with different NiCr content were prepared using the plasma spraying system. Second, the erosion rate of NiCr + Cr3C2–NiCr coatings in relation to the impact angle and the concentration of NiCr was measured by an air jet erosion test system, the microhardness was measured on the polished cross-section, and the erosion morphology was observed by SEM and analysed. Erosion behavior analysis showed that the NiCr + Cr3C2–NiCr coatings exhibited the coupling erosion wear mechanism of high toughness and high hardness, where the dominant characteristic was depending on the concentration of NiCr. Then, a tangential functional gradient coating structure was proposed by combining the excellent erosion wear resistance of ductile and brittle materials at varying impact angles, and a semi-theoretical erosion rate model considering the influence of the NiCr concentration was established based on the deformation wear theory. The erosion rate model was validated by experiments which showed the error was within 9.15%. Consequently, the erosion rate can be regulated on demand along the entire eroded surface, which significantly improves the erosion resistance of cermet at medium and high impact angles, thus prolonging the residual life of remanufactured impeller.

The differentiation of oligodendroglia from oligodendrocyte precursor cells (OPCs) to complex and extensive myelinating oligodendrocytes (OLs) is a multistep process that involves large-scale morphological changes with significant strain on the cytoskeleton. While key chromatin and transcriptional regulators of differentiation have been identified, their target genes responsible for the morphological changes occurring during OL myelination are still largely unknown. Here, we show that the regulator of focal adhesion, Tensin3 (Tns3), is a direct target gene of Olig2, Chd7, and Chd8, transcriptional regulators of OL differentiation. Tns3 is transiently upregulated and localized to cell processes of immature OLs, together with integrin-β1, a key mediator of survival at this transient stage. Constitutive Tns3 loss of function leads to reduced viability in mouse and humans, with surviving knockout mice still expressing Tns3 in oligodendroglia. Acute deletion of Tns3 in vivo, either in postnatal neural stem cells (NSCs) or in OPCs, leads to a twofold reduction in OL numbers. We find that the transient upregulation of Tns3 is required to protect differentiating OPCs and immature OLs from cell death by preventing the upregulation of p53, a key regulator of apoptosis. Altogether, our findings reveal a specific time window during which transcriptional upregulation of Tns3 in immature OLs is required for OL differentiation likely by mediating integrin-β1 survival signaling to the actin cytoskeleton as OL undergo the large morphological changes required for their terminal differentiation.

To improve the surface corrosion resistance of 42CrMo4 high-strength steel used in a marine environment, this article studied the effects of hard turning on the surface integrity and corrosion resistance of 42CrMo4 high-strength steel through the single factor experimental method, namely hard turning, polarization corrosion, electrochemical impedance spectroscopy, potentiodynamic polarization curve, and salt spray tests. The results indicated that the surface integrity was modified by the hard turning, with a surface roughness lower than Ra 0.8 μm, decreased surface microhardness, fine and uniform surface microstructure, and dominant surface residual compressive stress. The hard turning process was feasible to strengthen the surface corrosion resistance of 42CrMo4 high-strength steel. The better corrosion resistance of the surface layer than that of the substrate material can be ascribed to the uniform carbides and compact microstructure. The corrosion resistance varied with cutting speeds as a result of the changed surface microhardness and residual compressive stress, varied with feed rates as a result of the changed surface roughness, and varied with cutting depths as a result of the changed surface residual compressive stress, respectively. The surface integrity with smaller surface roughness and microhardness and bigger surface residual compressive stress was beneficial for corrosion resistance.

Abstract Background Several studies have indicated that skin holds promise as a potential sample for detecting pathological α-Syn and serving as a diagnostic biomarker for α-synucleinopathies. Despite reports in Chinese PD patients, comprehensive research on skin α-Syn detection using RT-QuIC is lacking. Objective This study aimed to evaluate the diagnostic performance of skin samples using RT-QuIC from PD patients in the Chinese population. Methods Patients with sporadic PD and controls were included according to the British PD Association Brain Bank diagnostic criteria. The seeding activity of misfolded α-Syn in these skin samples was detected using the RT-QuIC assay after protein extraction. Biochemical and morphological analyses of RT-QuIC products were conducted by atomic force microscopy, transmission electron microscopy, Congo red staining, and dot blot analysis. Result 30 patients clinically diagnosed with PD and 28 controls with non-α-synucleinopathies were included in this study. 28 of 30 PD patients demonstrated positive α-Syn seeding activity by RT-QuIC assay. In contrast, no α-Syn seeding activity was detected in the 28 control samples, with an overall sensitivity and specificity of 93.3% and 100%, respectively (P

Abstract Background Commonly clinically diagnosed with relapsing polychondritis (RP), vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) is a recently identified autoinflammatory disease caused by UBA1 somatic mutations. The low frequency and dynamic changes challenge the accurate detection of somatic mutations. The present study monitored these mutations in Chinese patients with RP. We included 44 patients with RP. Sanger sequencing of UBA1 was performed using genomic DNA from peripheral blood. Droplet digital polymerase chain reaction (ddPCR) was performed to screen low-prevalence somatic variants. Results Multiple ddPCR detections were performed using available blood samples collected at different follow-up time points. Three male patients were UBA1 somatic mutation carriers. Sanger sequencing detected the somatic UBA1 variant c.122T > C (p.Met41Thr) in two male patients. Initial ddPCR confirmed the variant in the two patients, with allele fractions of 73.75% and 88.46%, respectively, while yielding negative results in other patients. Subsequent ddPCR detected the somatic variant (c.122T > C) with low prevalence (1.02%) in another male patient from blood samples collected at a different time point, and confirmed dynamically fractional abundance in one patient with VEXAS, with allele fractions of 73.75%, 61.28%, 65.01%, and 73.75%. Nine patients assessed by ddPCR at different time points remained negative. Conclusion We report UBA1 variants in patients with RP in the Chinese population for the first time. Multiple ddPCR detections from samples collected at different time points can enhance sensitivity and should be considered for patients with initial negative ddPCR results.

BackgroundCutaneous phosphorylated alpha-synuclein (p-α-syn) deposition is an important biomarker of idiopathic Parkinson’s disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD.ObjectiveThis study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with CHCHD2 or RAB39B mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies.MethodsWe performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with CHCHD2 mutations, two patients with RAB39B mutations, 16 patients with PRKN mutations, 14 patients with LRRK2 mutations, five patients with GBA mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy.ResultsP-α-syn was deposited in the peripheral cutaneous nerves of PD patients with CHCHD2, LRRK2, or GBA mutations but not in those with RAB39B or PRKN mutations. There were no significant differences in the location or rate of α-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous α-synuclein SAA analysis of iPD and LRRK2 and GBA mutation patients revealed prion-like activity.ConclusionP-α-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.

Over 50 genetic human disorders are attributed to the irregular expansion of microsatellites. These expanded microsatellite sequences can experience bidirectional transcription, leading to new reading frames. Beyond the standard AUG initiation or adjacent start codons, they are translated into proteins characterized by disease-causing amino acid repeats through repeat-associated non-AUG translation. Despite its significance, there's a discernible gap in comprehensive and objective articles on RAN translation. This study endeavors to evaluate and delineate the contemporary landscape and progress of RAN translation research via a bibliometric analysis. We sourced literature on RAN translation from the Web of Science Core Collection. Utilizing two bibliometric analysis tools, CiteSpace and VOSviewer, we gauged individual impacts and interactions by examining annual publications, journals, co-cited journals, countries/regions, institutions, authors, and co-cited authors. Following this, we assessed the co-occurrence and bursts of keywords and co-cited references to pinpoint research hotspots and trending in RAN translation. Between 2011 and 2022, 1317 authors across 359 institutions from 34 countries/regions contributed to 250 publications on RAN translation, spread across 118 academic journals. This article presents a systematic, objective, and comprehensive analysis of the current literature on RAN translation. Our findings emphasize that mechanisms related to C9orf72 ALS/FTD are pivotal topics in the realm of RAN translation, with cellular stress and the utilization of small molecule marking the trending research areas.

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) is a novel alternative to perfluorooctane sulfonate (PFOS), with environmental health risks largely unknown. The present study aims to unravel the adipogenesis effects and underlying molecular initiating events of OBS, which are crucial for understanding and predicting its adverse outcome. In undifferentiated human mesenchymal stem cells (hMSCs), exposure to 1–100 nM of OBS for 7 days stimulated reactive oxygen species production. In the subsequent multipotent differentiation, hMSCs favored adipogenesis and repressed osteogenesis. The point of departure (PoD) for cellular responses of OBS was 38.85 nM, higher than PFOS (0.39 nM). Notably, OBS/PFOS co-exposure inhibited osteogenesis and synergistically promoted adipogenesis. Consistently, the expression of adipogenic marker genes was up-regulated, while that of osteogenic marker genes was down-regulated. The decreased adiponectin and elevated tumor necrosis factor α (TNFα) secretion were observed in differentiated cells exposed to the mixture of OBS and PFOS. The co-treatment of a peroxisome proliferator-activated receptor γ (PPARγ) antagonist alleviated the adipogenic effects of PFOS and its combination with OBS. Moreover, OBS/PFOS co-exposure induced peroxisome PPARγ activation in reporter gene assays, and increased formation of PPARγ - retinoid X receptor α (RXRα) heterodimers measured by co-immunoprecipitation assays. Molecular docking showed interaction energy of OBS (-20.7 kcal/mol) with intact PPARγ-RXRα complex was lower than that of PFOS (-25.9 kcal/mol). Overall, single OBS exhibited lower potency in inducing adipogenesis but is comparable to PFOS in repressing osteogenesis, whereas OBS/PFOS co-exposure increases interaction with PPARγ-RXRα heterodimers, resulting in the synergistic activation of PPARγ, ultimately enhancing adipogenesis at the expense of osteogenic differentiation. The results indicate the potential health risks of increased obesity and decreased bone density caused by OBS and its co-exposure with PFOS, as well as other perfluorinated alkylated substances mixtures.

Abstract Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx. Dysosmia is regarded as an early sign of coronavirus disease 2019 (COVID-19), and nasal swabs are the gold standard for the detection. By nasal swabs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids can be cyclically amplified and detected using real-time reverse transcriptase-polymerase chain reaction after sampling. Similarly, olfactory dysfunction precedes the onset of typical clinical manifestations by several years in prion diseases and other neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. In neurodegenerative diseases, nasal swab tests are currently being explored using seed amplification assay (SAA) of pathogenic misfolded proteins, such as prion, α-synuclein, and tau. These misfolded proteins can serve as templates for the conformational change of other copies from the native form into the same misfolded form in a prion-like manner. SAA for misfolded prion-like proteins from nasal swab extracts has been developed, conceptually analogous to PCR, showing high sensitivity and specificity for molecular diagnosis of degenerative diseases even in the prodromal stage. Cyclic amplification assay of nasal swab extracts is an attractive and feasible method for accurate and non-invasive detection of trace amount of pathogenic substances for screening and diagnosis of neurodegenerative disease. Graphical Abstract

Spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease, is the most common dominantly inherited ataxia. SCA3 is caused by a CAG repeat expansion in the ATXN3 gene that encodes an expanded tract of polyglutamine in the disease protein ataxin-3 (ATXN3). As a deubiquitinating enzyme, ATXN3 regulates numerous cellular processes including proteasome- and autophagy-mediated protein degradation. In SCA3 disease brain, polyQ-expanded ATXN3 accumulates with other cellular constituents, including ubiquitin (Ub)-modified proteins, in select areas like the cerebellum and the brainstem, but whether pathogenic ATXN3 affects the abundance of ubiquitinated species is unknown. Here, in mouse and cellular models of SCA3, we investigated whether elimination of murine Atxn3 or expression of wild-type or polyQ-expanded human ATXN3 alters soluble levels of overall ubiquitination, as well as K48-linked (K48-Ub) and K63-linked (K63-Ub) chains. Levels of ubiquitination were assessed in the cerebellum and brainstem of 7- and 47-week-old Atxn3 knockout and SCA3 transgenic mice, and also in relevant mouse and human cell lines. In older mice, we observed that wild-type ATXN3 impacts the cerebellar levels of K48-Ub proteins. In contrast, pathogenic ATXN3 leads to decreased brainstem abundance of K48-Ub species in younger mice and changes in both cerebellar and brainstem K63-Ub levels in an age-dependent manner: younger SCA3 mice have higher levels of K63-Ub while older mice have lower levels of K63-Ub compared to controls. Human SCA3 neuronal progenitor cells also show a relative increase in K63-Ub proteins upon autophagy inhibition. We conclude that wild-type and mutant ATXN3 differentially impact K48-Ub- and K63-Ub-modified proteins in the brain in a region- and age-dependent manner.

As the primary molecular target, there is still a gap between the peroxisome proliferator-activated receptors (PPARs) regulation and the adverse health effects caused by per- and polyfluoroalkyl substances (PFASs). The effects of PFASs on cellular differentiation regulated by PPARs is likely significant given the association of PFASs exposure with obesity and decreased bone density. Human mesenchymal stem cells (hMSCs) were used as an in vitro model to assess the roles of PPAR subtypes in the multipotent differentiation of hMSCs affected by perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA) and their replacement compounds. PFASs increased the expression of three PPAR subtypes in proliferating and differentiating hMSCs. Meanwhile, PFOS and PFOA decreased osteogenesis, enhanced adipogenesis, and increased bone turnover in hMSCs. Similarly, PFOA alternatives, hexafluoropropylene oxide dimer acid (HFPO-DA) and hexafluoropropylene oxide trimer acid (HFPO-TA), exhibited similar or even higher potency in affecting stem cell differentiation compared with PFOA. Perfluorohexanesulfonate (PFHxS) inhibited osteogenesis with comparable potency to PFOS. In contrast, 6:2 chlorinated poly-fluoroalkyl ether sulfonate (6:2Cl-PFESA) enhanced osteogenesis. PPARβ expression is significantly positively correlated with osteogenesis and osteoprotegerin (OPG) secretion in 6:2Cl-PFESA treated cells. shRNA knockdown of PPARβ remarkably reversed the osteogenic effects of 6:2Cl-PFESA and enhanced the adipogenic effects of the six chemicals. The results suggested that the adverse effects and relative potency of PFASs on the multipotent differentiation of hMSCs were dependent on the integrated action of the three PPAR subtypes, which facilitates a better understanding of the molecular initiating events of PFASs. The present study may well explain the mechanism of the decreased bone density and increased obesity incidence among those exposed to legacy PFASs, and indicates the necessity of further health risk assessment for the alternatives.

The accumulation and deposition of misfolded α-synuclein (α-Syn) aggregates in the brain is the central event in the pathogenesis of α-synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple-system atrophy. Currently, the diagnosis of these diseases mainly relies on the recognition of advanced clinical manifestations. Differential diagnosis among the various α-synucleinopathies subtypes remains challenging. Misfolded α-Syn can template its native counterpart into the same misfolded one within or between cells, behaving as a prion-like seeding. Protein-misfolding cyclic amplification and real-time quaking-induced conversion are ultrasensitive protein amplification assays initially used for the detection of prion diseases. Both assays showed high sensitivity and specificity in detection of α-synucleinopathies even in the pre-clinical stage recently. Herein, we collectively reviewed the prion-like properties of α-Syn and critically assessed the detection techniques of α-Syn-seeding activity. The progress of test tissues, which tend to be less invasive, is presented, particularly nasal swab, which is now widely known owing to the global fight against coronavirus disease 2019. We highlight the clinical application of α-Syn seeding in early and non-invasive diagnosis. Moreover, some promising therapeutic perspectives and clinical trials targeting α-Syn-seeding mechanisms are presented.